Fabrication of a 3D Printed PCL Nerve Guide: In Vitro and In Vivo Testing.

Nerve guides are medical devices designed to guide proximal and distal ends of injured peripheral nerves in order to assist regeneration of the damaged nerves. A 3D-printed polycaprolactone (PCL) nerve guide using an aligned gelatin-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) electrospun mat, seeded with PC12 and Schwann cells (SCs) is produced. During characterization with microCT and SEM porosity (55%), pore sizes (675 ± 40 µm), and fiber diameters (382 ± 25 µm) are determined. Electrospun fibers have degree of alignment of 7°, indicating high potential for guidance. On Day 14, PC12 cells migrated from proximal to distal end of nerve guide when SCs are seeded on the guide. After 28 days, over 95% of PC12 are alive and aligned. PC12 cells express early differentiation marker beta-tubulin 10 times more than late marker NeuN. In a 10 mm rat sciatic nerve injury, functional recovery evaluated by using static sciatic index (SSI) is observed in mat-free guides and guides containing mat and SCs. Nerve conduction velocities are also improved in these groups. Histological stainings showed tissue growth around nerve guides with highest new tissue organization being observed with mat and cell-free guides. These suggest 3D-printed PCL nerve guides have significant potential for treatment of peripheral nerve injuries.

3D and 4D Printing of Polymers for Tissue Engineering Applications.

Three-dimensional (3D) and Four-dimensional (4D) printing emerged as the next generation of fabrication techniques, spanning across various research areas, such as engineering, chemistry, biology, computer science, and materials science. Three-dimensional printing enables the fabrication of complex forms with high precision, through a layer-by-layer addition of different materials. Use of intelligent materials which change shape or color, produce an electrical current, become bioactive, or perform an intended function in response to an external stimulus, paves the way for the production of dynamic 3D structures, which is now called 4D printing. 3D and 4D printing techniques have great potential in the production of scaffolds to be applied in tissue engineering, especially in constructing patient specific scaffolds. Furthermore, physical and chemical guidance cues can be printed with these methods to improve the extent and rate of targeted tissue regeneration. This review presents a comprehensive survey of 3D and 4D printing methods, and the advantage of their use in tissue regeneration over other scaffold production approaches.

A novel GelMA-pHEMA hydrogel nerve guide for the treatment of peripheral nerve damages.

Damage to the nervous system due to age, diseases or trauma may inhibit signal transfer along the nervous system. Nerve guides are used to treat these injuries by bridging the proximal and the distal end together. The design of the guide is very important for the reconnection of the severed axons. Methacrylated gelatin-poly(2-hydroxyethylmethacrylate) (GelMA-pHEMA) hydrogel was produced as the outer part of the nerve guide. pHEMA was added in various amounts into GelMA and increased the mechanical strength which is needed for the suturability of the guide. Porosity (15-70%), pore size (10-35 µm), water content (42-92%), and mechanical strength (65-710 kPa) of GelMA-pHEMA hydrogels were found to be suitable for nerve tissue engineering applications. Schwann cells attached and proliferated on GelMA, GelMA-pHEMA (5:5), and pHEMA hydrogels. Providing guidance is very important in the development of a nerve guide due to the anisotropic nature of the nerve tissue. Therefore, gelatin-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) aligned fiber mats were used inside of the nerve guide. High degree of alignment with low deviation (7°) of this mats provided PC12 cell alignment throughout the fibers. Combination of GelMA-pHEMA (5:5) hydrogel and gelatin-PHBV aligned mat would provide an ideal nerve guide for the treatment of peripheral nerve damages.